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28. Clinical and Pathological Study of Polyomavirus-Associated Nephropathy after Renal Transplantation

Author

Ni Xuefeng, Wen Jiqiu, Chen Jinsong, Li xu, Xie Kenan, Ji Shu-Ming, Cheng Dongrui, and Liu Zhi-hong

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Urinary system, Immunosuppression, Decoy cells, medicine.disease, Nephropathy, Transplantation, Fibrosis, Biopsy, medicine, Renal biopsy, medicine.symptom, business
Abstract

Polyomavirus infection has emerged as an important cause of polyomavirus-associated nephropathy (PVAN) leading to allograft dysfunction and loss. The aim of this study is to investigate pathological features and clinical characteristics of PVAN. We prospectively investigated 351 renal allografts performed in Jinling Hospital. PVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. 31 patients were diagnosed with PVAN (8.8%). The patients with PVAN typically presented as allograft dysfunction with an asymptomatic rise in serum creatinine about 3 to 39 months posttransplant. Urinary decoy cells were positive in 4 patients (12.9%). The histologic changes of PVAN are not pathognomonic and can be mistaken for allograft rejection, i.e. tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis, tubular atrophy and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining is positive in allograft. CD3, CD4, CD8, CD68 positive cells are increased in PVAN group than the non-PVAN group, but none of HLA-DR and IL-2R expression is positive in PVAN patients. MPA AUC 0-12 and TAC trough levels are increased in PVAN group than non-PVAN group at biopsy. We have treated 31 patients with biopsy-proven PVAN with leflunomide. Increased intensity of immunosuppression appears to increase the likelihood of PVAN. The definitive diagnosis of PVAN requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of PVAN.

Published
2014

29. CD20+ B-cell infiltration is related to the time after transplant and poor prognosis of acute cellular rejection in renal transplant

Author

Ji Shu-Ming, Cheng Dongrui, Chen Jinsong, Liu Zhi-hong, Zhang Mingchao, and Wen Jiqiu

Subjects
Adult, Graft Rejection, Male, Pathology, medicine.medical_specialty, Hyalin, Time Factors, Tubular atrophy, Kaplan-Meier Estimate, Kidney, Young Adult, Risk Factors, medicine, Humans, Least-Squares Analysis, Kidney transplantation, B cell, Proportional Hazards Models, Retrospective Studies, Transplantation, B-Lymphocytes, Immunity, Cellular, Chi-Square Distribution, business.industry, CD68, Kidney metabolism, HLA-DR Antigens, Middle Aged, medicine.disease, Antigens, CD20, Kidney Transplantation, medicine.anatomical_structure, Treatment Outcome, Acute Disease, Multivariate Analysis, Female, business, Infiltration (medical), CD8, Biomarkers
Abstract

Objectives This study sought to determine the relation between CD20+ B-cell infiltration and time after transplant and outcome of acute cellular rejection in renal allografts. Materials and methods Fifty-five patients with acute cellular rejection were categorized into 3 groups: very early, early, and late rejection. The density of CD4+, CD8+, CD20+, and CD68+ cells and HLA-DR expression were characterized and quantified using immunohistochemical staining. Histologic changes were compared between high-density and low-density CD20+ B-cell groups. Poor prognosis factors were analyzed with Cox proportional regression. Results Density of CD20+ cells in the very-early rejection group was lower than it was in the early- and late-acute rejection groups (P = .03); the density of CD4+, CD8+, and CD68+ cells and HLA-DR expression did not differ between the groups. Mesangial matrix increase, tubular atrophy, arteriolar hyaline thickening, and tubulitis were more prevalent in the high CD20+ density group. Cox regression analysis demonstrated that HLA-DR expression on the tubules, arteriolar hyaline thickening, and CD20+ cell density were associated with an elevated risk of acute cellular rejection. Conclusions Expansion aggregation of CD20+ B cells occurred mostly after 2 weeks. When combined with HLA-DR expression and arteriolar hyaline thickening, these influence the outcome of acute cellular rejection in renal allograft.

Published
2013

37. HLA-DR overexpression in tubules of renal allografts during early and late renal allograft injuries.

Author

Wen J, Zhang M, Chen J, Zeng C, Cheng D, and Liu ZH

Subjects
Adolescent, Adult, Aged, Allografts, Biomarkers metabolism, Biopsy, Female, Follow-Up Studies, Graft Rejection epidemiology, Graft Rejection pathology, Humans, Incidence, Kidney Tubules pathology, Male, Middle Aged, Retrospective Studies, Time Factors, Young Adult, Graft Rejection metabolism, HLA-DR Antigens metabolism, Kidney Transplantation, Kidney Tubules metabolism, Up-Regulation
Abstract

Objectives: We sought to discover which types of injuries were related to human leukocyte antigen DR expression in acute rejection and late chronic injury in renal allografts., Materials and Methods: Ninety-two recipients were separated into the early acute rejection group, the late monocyte infiltration group, and the late chronic injury group. Ten subjects with acute cellular rejection received a repeat biopsy. All samples were stained with CD4, CD8, CD20, CD68, and human leukocyte antigen DR by immunochemical staining. Levels of these markers were compared among the subgroups of each group., Results: Human leukocyte antigen DR expression was greater in the early C4d-negative acute rejection group than it was in the early C4d-positive acute rejection group. Human leukocyte antigen DR expression was greater during acute rejection than that was on a repeat biopsy. Human leukocyte antigen DR expression was accord with the infiltration of monocyte infiltration in the acute cellular rejection group. Human leukocyte antigen DR expression was greater during late acute rejection than it was in BK virus nephropathy, which was not in accord with monocyte infiltration. Human leukocyte antigen DR expression was greater during chronic rejection than it was in IgAN, BK virus nephropathy, and TA/IF groups, and even in tubular atrophy., Conclusions: Human leukocyte antigen DR expression in renal tubular cells was associated with early acute cellular rejection and was in accord with monocyte infiltration. Human leukocyte antigen DR expression in renal tubular cells during the late phase (especially in tubular atrophy) was a marker of chronic rejection, but was not in accord with monocyte infiltration in renal allografts.

Published
2013
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38. Special malignancy pattern in Chinese renal transplantation recipients: a single center experience and literature review.

Author

Sun Q, Li X, Cheng D, He Q, Chen J, Ji S, and Liu Z

Subjects
Adolescent, Adult, Aged, Child, China epidemiology, Digestive System Neoplasms epidemiology, Female, Follow-Up Studies, Humans, Incidence, Kidney Failure, Chronic surgery, Liver Neoplasms epidemiology, Male, Middle Aged, Prognosis, Retrospective Studies, Review Literature as Topic, Skin Neoplasms epidemiology, Transplantation, Homologous, Urinary Bladder Neoplasms epidemiology, Young Adult, Digestive System Neoplasms etiology, Kidney Failure, Chronic complications, Kidney Transplantation adverse effects, Liver Neoplasms etiology, Postoperative Complications, Skin Neoplasms etiology, Urinary Bladder Neoplasms etiology
Abstract

Malignancy is one of the main complications after renal transplantation but the situation in Chinese renal allograft recipients remains an enigma. We therefore reviewed 1,000 (8,531 person-years follow-up) renal allograft recipients from Jinling Hospital, Nanjing University, revealing an incidence rate of 2.4% of post-transplant malignancies, with a standardized incidence ratio (SIR) of 17.8 (95% C.I.: 16.7-18.8); the standardized rate is 1.67%, compared with 0.29% in the general population. However, our group demonstrated an extremely low incidence of skin cancer, which dominates in western countries. To confirm the findings, we reviewed the literature on post-transplant malignancies in Chinese renal allograft recipients, covering 296 malignancies in 18,548 renal transplant recipients in 21 reports. The top three most common sites of malignancies were the digestive tract, bladder and liver. The incidence of skin cancer was very low in most centers. These data show that Chinese renal allograft recipients have a unique spectrum of post-transplant malignancies, with an extremely very low incidence of skin cancer as compared to populations from western countries.

Published
2011

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